Dispersal of weaponizable bacterial pathogens among foreign states and terrorists poses a significant military and public health threat. For example, Bacillus anthracis was used by a terrorist in the United States, Saddam Hussein's Iraq was known to have had bioweapons programs involving anthrax and brucellosis, and Russia has an extensive biowarfare program involving a wide array of natural and engineered bacteria. Conventional classes of antibiotics are generally effective against pathogens such as Bacillus anthracis, but several challenges demand that new classes of broad-spectrum antibiotics be developed for troop preparedness and biodefense. First, the natural spread of antibiotic resistance genes in bacterial populations has lead to decreasing options for antibiotic therapy. Many natural isolates of B. anthracis are now resistant to penicillin, and for other pathogens, such as Brucella species and Mycobacterium tuberculosis, treatment is often limited to drugs with serious risks or side effects. Second, the intentional engineering of resistance to known classes of antibiotics into biowarfare agents could significantly increase the severity and duration of infection due to biological attacks. Third, relatively benign pathogens can be engineered to kill infected patients upon treatment with conventional antibiotics. For example, pertussis toxin could be cloned under the control of a tetracycline-inducible promoter in Chlamydia so that the standard antibiotic treatment leads to rapid death. Fourth, unknown species or species for which there is not a rapid diagnostic test may be developed as biowarfare agents, requiring treatment before a diagnosis has been made. Novel broad-spectrum antibiotics could be used to treat unknown pathogens and pathogens resistant to known classes of antibiotics.
There is thus a need in the art to provide novel agents which have antibacterial activity to which bacteria do not develop resistance.